The purpose of the proposed research is to further define the responses of T lymphocytes to chemically defined antigenic determinants. Up to the present time, this project has primarily involved the use of guinea pigs as experimental animals. In the past year we have changed over to mice, for a number of reasons. This has necessitated a large number of preliminary experiments to determine ways of sensitizing the animals to produce in vitro responses to haptenated proteins. We have now apparently succeeded in doing this, and we propose to test the following questions in the coming period of time: Do mouse T cells sensitized to the hapten 2,4,6-trinitrophenyl (TNP) also respond to the hapten 2,4-dinitrophenyl (DNP), or are they more specific than anti-TNP antibody, which does so cross-react? Does an anti-idiotypic antibody directed at what we think is the dominant (probably germ line) anti-DNP idiotype of certain mouse strains block the response of DNP-sensitized T cells? If so, what is the strain distribution of this T cell idiotype? What do surface receptors that bind to the anti-idiotype look like biochemically? Will the anti-idiotype stimulate the T cells in vivo or in vitro? What happens to helper T cells for an anti-DNP antibody response when they are exposed to the anti-idiotype? From these questions we hope to gain further understanding of the nature of T cell receptors for antigen, and the regulatory interactions in T cell and B cell responses to defined antigenic determinants. This, in turn, should be applicable to the regulation of antibody responses in clinically relevant situations, most particularly to IgE antibody responses.